Diallyl Trisulfide Inhibits Growth of NCI-H460 in Vitro and in Vivo, and Ameliorates Cisplatin-Induced Oxidative Injury in the Treatment of Lung Carcinoma in Xenograft Mice

作者：Jiang, Xiaoyan; Zhu, Xiaosong; Liu, Na; Xu, Hongya; Zhao, Zhongxi^*; Li, Siying^*; Li, Shanzhong; Cai, Jianhua; Cao, Jimin

来源：International Journal of Biological Sciences, 2017, 13(2): 167-178.

DOI：10.7150/ijbs.16828

• Diallyl trisulfide
• cisplatin
• lung carcinoma
• enhanced effect
• attenuate side effect

Diallyl trisulfide ( DATS), an organosulfuric component of garlic oil, exhibits potential anticancer and chemopreventive effects. Cisplatin ( DDP), a common chemotherapeutic agent, has provided great therapeutic contributions to treating solid tumors, but with serious side effects. Here, we verified the anti- tumor properties of DATS on lung cancer in vitro and in vivo, and evaluated synergistic effects of DATS combined with DDP on the NCI- H460 xenograft model. Significantly decreased cell viabilities, cell cycle G(1) arrest, and apoptosis induction were observed in DATS treated NCI- H460 cells ( p< 0.05). And injection of DATS ( 30 or 40 mg/ kg) to female Balb/ c mice significantly inhibited the growth of human NCI- H460 cell tumor xenograft ( p< 0.001). Moreover, DATS in combination with DDP exhibited enhanced anti- tumor activity via induction of apoptosis. Apoptosis pathways were confirmed by modulation of p53, Bcl- 2 family members; induction of active caspase- 3/ 8/ 9 and activation of JNK- and p38- MAPK pathways. Interestedly, DATS+ DDP administration exerted fewer side effects, such as suppressing the weight loss and ameliorating DDP- induced oxidative injury, especially in renal parenchyma. In addition, increased E- cadherin and decreased MMP- 9 expression levels were observed in DATS- treated tumor tissues. These studies provide supports that DATS might be a potential candidate for combination with DDP in cancer treatment.

• 出版日期2017
• 单位山东大学